DDX3-mediated translational activation drives β-catenin signaling and cancer cell motility

Abstract

The DEAD box RNA helicase DDX3 regulates multiple steps in gene expression and also can mediate cell signaling. Dysregulation of DDX3 has been observed in various cancers, and, notably, its mutations are particularly associated with the wingless (Wnt) type of medulloblastoma. DDX3 can promote cell cycle progression, prevent apoptosis, and increase cell migration in some cancerous cells. Detailed mechanisms by which DDX3 modulates cell adhesion and migration and even the epithelial-mesenchymal transition have only just begun to emerge. We recently demonstrated that DDX3 generally modulates cell adhesion and migration properties in various cell lines, essentially via its activity in promoting the translation of Rac1 mRNA. Moreover, our results indicate that DDX3-activated Rac1 translation is required for Wnt-β-catenin signaling and supports the cell adhesion and migration activities of metastatic cancer cells. This DDX3-Rac1-b-catenin pathway suggests a new role for DDX3 in the Wnt type, and perhaps also other types, of medulloblastoma.